神经元和星形胶质细胞钙信号异常参与阿尔茨海默病研究进展

Recent advance in abnormal neuronal and astrocytic calcium signalw involved in Alzheimer's disease progression

阿尔茨海默病(AD)患者或AD动物模型大脑中β-淀粉样蛋白(Aβ)、tau蛋白、早老素(PS)1、PS2和载脂蛋白E4(ApoE4)等会影响神经元细胞膜、内质网膜和线粒体膜上的钙通道,最终导致神经元的钙稳态失衡。Aβ还可以作用于星形胶质细胞(AS)内质网引起AS内钙信号异常。而大脑异常的钙信号反过来会作用于神经元和AS,促进Aβ的产生、tau蛋白磷酸化,从而加重AD病情。本研究围绕AD中神经元和AS内钙信号的变化进行综述,以期阐明神经元和AS内钙稳态失衡与AD病理学特征之间的联系,为AD的预防和治疗提供新思路。

In the brains of patients with Alzheimer's disease(AD)or AD animal models,β-amyloid(Aβ),tau protein,presenilin(PS)1,PS2 and apolipoprotein E4(ApoE4)would affect the calcium channels on neuronal cell membrane,endoplasmic reticulum membrane and mitochondrial membrane,and eventually lead to the imbalance of calcium homeostasis in neurons.Aβcan also act on the endoplasmic reticulum of astrocytes and cause abnormal calcium signal.Abnormal calcium signals in the brain in turn act on neurons and promote Aβand tau protein phosphorylation,which aggravates the disease.This study focuses on the changes of calcium signals in neurons and astrocytes in AD,in order to clarify the relationship between the calcium dyshomeostasis in neurons and astrocytes and the pathogenesis of AD,thus provides new idea for the prevention and treatment of AD.